The present invention relates to an improved vascular prosthesis and, more particularly, to a non-woven vascular prosthesis having improved biological, physical and mechanical properties and improved drug-delivery capability.
Tubular prostheses are commonly used as vascular grafts to replace or bypass damaged or diseased veins and arteries. When replacing blood vessels, grafts should have radial tensile strength sufficient to resist tearing and collapse in response to the pulsating pressure of the blood flowing therethrough. The elastic properties of grafts are crucial in order to allow conformation to the complex geometry of the body. Therewithal, grafts should be able to bend without breaking and without kinking, in order to ensure continues blood flow.
Artificial blood vessels and vascular prostheses are well known in the art. In particular, prosthetic devices made of polymer materials which typically exhibit a microporous structure that in general allows healthy tissue growth and cell endothelization, thus contributing to the long term healing and patency of the prostheses. Grafts having sufficient porous structure tend to promote tissue ingrowth and cell endothelization along the inner surface thereof. Increasing the porosity of vascular grafts leads to high permeability to blood during and following implantation. A typical method for avoiding severe blood leakage during implantation, is to clot the graft before implantation by patient blood or a biodegradable component such as albumin, gelatin, collagen or fibrin. Another disadvantage of highly porous vascular grafts, is a considerable reduction of the mechanical and tensile strength of the graft, and as a consequence the ability of the graft to remain in the proper position inside the body vasculature becomes weak. Furthermore, low mechanical and tensile strength may even lead to tearing of the graft. Examples for highly porous grafts are polyethylene terephtalat (PET) vascular prostheses fabricated as woven or knitted textiles which are disclosed in, for example, U.S. Pat. Nos. 5,527,353; 4,441,215; 4,695,280; and 5,584,875.
In a natural arterial tissue, the diameter of the blood vessel may vary up to 15% as a function of blood pressure. This characteristic of natural blood vessels, named compliance, is of crucial importance when manufacturing an artificial blood vessel. A compliant wall should act as an elastic reservoir, absorbing energy during systole and releasing energy during diastole. A rigid vessel wall diminishes the pulsatile component of the diastolic recoil, thereby reducing the energy available for distal perfusion. It has been demonstrated experimentally that incompatible compliance of a vascular graft and the host artery is detrimental to graft performance [Baird R. N., Abbott W. M. “Pulsatile blood-flow in arterial grafts”, The Lancet, 1976; 30; 948-9; Abbott W. M., Megerman J. M. et al. “Effect of compliance mismatch upon vascular graft patency”, J. Vasc. Surg. 1987, 5; 376-82].
Over the years, efforts have been made to fabricate prosthetic grafts having compliance, which are similar to that found in human arteries [Reed A. M., Potter J, Szycher M., “A solution grade biostable polyurethane elastomer: Chronoflex AR” Journal of Biomaterials Applications 1994; 8:210-36; Edwards A, Carson R. J; Bowald S., “Development of microporous small bore vascular graft”, Journal of Biomaterials Applications 1995; 10:171-87]. Hence many vascular grafts are either available commercially, or presently under development [Brewster D. C., Rutherford R. B., “Prosthetic Grafts”, Vascular Surgery 4th ed. Philadelphia; Saunders W. B., 1995; 492-521; Quinones-Baldrich W. J., Busutill R. W., Baker I. D. et al. “Is the preferential use of PTFE grafts for femoropopliteal bypass justified?”, J. Vasc. Surg. 1988; 219-228]. However, no known graft material has satisfactory compliance properties.
Large and moderate diameter, vascular prostheses are typically made of expanded polytetrafluorethylene (ePTFE), by extrusion, drawing and sintering process to produce a tube with a porous wall. Grafts made of ePTFE and methods for the production thereof are found, for example, in U.S. Pat. Nos. 5,628,786; 4,306,318; and 5,061,276. In regard to improved mechanical strength of vascular grafts, different ePTFE grafts have been proposed, and can be found for example in U.S. Pat. No. 6,001,125, which relates to an implantable microporous ePTFE vascular prosthesis having multiple layers. An additional example is U.S. Pat. No. 5,628,786 which discloses a vascular graft formed of ePTFE having a reinforced structure that enables radial expansion of the graft and that stabilizes the graft against longitudinal compression. However, ePTFE suffer inherently from low compliance, which limit the use thereof when manufacturing vascular grafts.
Attempts have also been made to provide grafts characterized by both high compliance and high porosity, by the utilization of fiber polyurethanes. However, many polyurethanes, including those based on polycarbonate soft segments, have insufficient long-term biostability. Recently, siloxane-based aromatic polyurethanes have been developed, which have acceptable biostability even for thin fibers [In Vivo Degradation of Polyurethanes: Transmission FTIR Microscopic Characterization of Polyurethanes Sectioned by Cryomicroscopy. MaCarthy S. J. at al., Biomaterials 18, 1387 (1997); Polydimethylsiloxane (polyether-mixed macrodiol-based polymethane elastomers) biostability, Martin D. J. et al., Biomaterials, 21, 1021-1029 (2000); PCTAU 91/00270; PCT/AU 99/00236; PCTAU 98/00497; PP 9917].
Electrospinning is a method for the manufacture of ultra-thin synthetic fibers which reduces the number of technological operations and increases the stability of properties of the product being manufactured. In regard to vascular prostheses, electrospinning and electrospinning-like manufacturing methods are disclosed, for example, in U.S. Pat. Nos. 4,562,707, 4,645,414, 5,639,278, 5,723,004 and 5,948,018. According to the electrospinning method, fibers of a given length are formed during the process of polymer solution flow from capillary apertures under electric forces and fall on a receptor to form a non-woven polymer material, the basic properties of which may be effectively altered. Being electrically charged, the fibers fall on the receptor in a manner that minimizes the pore size deviation. As stated, high porosity may affect the mechanical and tensile strength of the graft.
There is thus a widely recognized need for, and it would be highly advantageous to have, a vascular prosthesis and method for production thereof, devoid of the above limitations.